Febuxostat treatment attenuates oxidative stress and inflammation due to ischemia-reperfusion injury through the necrotic pathway in skin flap of animal model

Odake, Kazuya; Tsujii, Masaya; Iino, Takahiro; Chiba, Katsura; Kataoka, Tetsuro; Sudo, Akihiro

doi:10.1016/j.freeradbiomed.2021.10.033

Cited by 20 publications

(13 citation statements)

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“…Antioxidant vitamins in high doses neutralize the negative effects of the oxidative bursts during reperfusion by either neutralizing the effect of ROS or by preventing the bursts from occurring. 38 Vitamin C has already been studied for limiting the effects of RHR injury in both animal models and in vitro studies. 39 In contrast, the role of retinol in countering RHR injury has not been studied to date.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Vitamins have been extensively evaluated for the treatment of RHR injury, showing protective characteristics. Antioxidant vitamins in high doses neutralize the negative effects of the oxidative bursts during reperfusion by either neutralizing the effect of ROS or by preventing the bursts from occurring . Vitamin C has already been studied for limiting the effects of RHR injury in both animal models and in vitro studies .…”

Section: Resultsmentioning

confidence: 99%

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Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Salih

Asif

Samantasinghar

et al. 2022

ACS Biomater. Sci. Eng.

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Renal ischemic-reperfusion injury decreases the chances of long-term kidney graft survival and may lead to the loss of a transplanted kidney. During organ excision, the cycle of warm ischemia from the donor and cold ischemia is due to storage in a cold medium after revascularization following organ transplantation. The reperfusion of the kidney graft activates several pathways that generate reactive oxygen species, forming a hypoxic-reperfusion injury. Animal models are generally used to model and investigate renal hypoxic-reperfusion injury. However, these models face ethical concerns and present a lack of robustness and intraspecies genetic variations, among other limitations. We introduce a microfluidics-based renal hypoxic-reperfusion (RHR) injury-on-chip model to overcome current limitations. Primary human renal proximal tubular epithelial cells and primary human endothelial cells were cultured on the apical and basal sides of a porous membrane. Hypoxic and normoxic cell culture media were used to create the RHR injury-on-chip model. The disease model was validated by estimating various specific hypoxic biomarkers of RHR. Furthermore, retinol, ascorbic acid, and combinational doses were tested to devise a therapeutic solution for RHR. We found that combinational vitamin therapy can decrease the chances of RHR injury. The proposed RHR injury-on-chip model can serve as an alternative to animal testing for injury investigation and the identification of new therapies.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Salih

Asif

Samantasinghar

et al. 2022

ACS Biomater. Sci. Eng.

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“…In the process of uric acid synthesis, XO is an essential enzyme responsible for the conversion of hypoxanthine to uric acid and the production of H 2 O 2 during this process, which further causes ROS (Kimura et al, 2021;Odake et al, 2021). The accumulation of ROS will act on mitochondria to activate apoptosis (Li et al, 2016).…”

Section: Uric Acid Pathway Inhibits Bmnpv By Activating Apoptosismentioning

confidence: 99%

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori

et al. 2023

Insect Molecular Biology

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The white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine‐fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests.

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“…3 During skin flap transplantation, there are different degrees of oxidative stress damage and various inflammatory reactions, which affect skin flap angiogenesis and cause some tissue cell necrosis, reducing the survival rate of the skin flap. 4,5 Currently, several drugs have been used to increase skin flap survival, such as calcitriol, aspirin, and vitamin C. [6][7][8] However, the therapeutic outcomes are unsatisfactory. Traditional Chinese medicine (TCM) has a unique advantage in the treatment of skin flap injury due to its multicenter and multitarget effects.…”

Section: Introductionmentioning

confidence: 99%

Fuyuan Huoxue Decoction Promotes Skin Flap Survival Via the P38MAPK/IKK/NF-κB Pathway in Rats

Zeng,

Yang,

Zhang

et al. 2023

Natural Product Communications

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Objective Fuyuan Huoxue decoction (FHD) is a traditional Chinese medicine that can promote blood circulation, inhibit inflammatory reactions and effectively relieve pain. This study investigated the effect of FHD on rat skin flap survival and the p38 MAPK/IKK/NF-κB pathway. Methods The pathological condition of the flap tissue was examined by H&E staining. The expression levels of CD34 and VEGF in skin flap tissues were examined by immunohistochemistry. The levels of TNF-α, IL-6, CRP, and HO-1, superoxide dismutase (SOD) activity, and MDA content were detected by ELISA. The protein expression levels of Bax, Bcl-2, cleaved-caspase 3, p-IKKαβ, p-p38, p-p65, α-SMA, CK14, CK15, and SOX2 were detected by western blotting. Results Fuyuan Huoxue decoction upregulated the levels of CD34, VEGF, and Bcl-2, downregulated the expression of TNF-α, IL-6, p-IKKαβ, P-P38, P-P65, Bax, and cleaved-caspase 3, increased the activity of SOD, and inhibited the level of MDA. In addition, FHD promoted the proliferation and differentiation of skin flap. Conclusions Fuyuan Huoxue decoction improved the survival of the rat skin flap model by regulating the p38MAPK/IKK/NF-κB signaling pathway, and the mechanism may be related to the promotion of skin flap proliferation, differentiation, and revascularization and the inhibition of inflammation and oxidative stress.

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Febuxostat treatment attenuates oxidative stress and inflammation due to ischemia-reperfusion injury through the necrotic pathway in skin flap of animal model

Cited by 20 publications

References 59 publications

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Renal Hypoxic Reperfusion Injury-on-Chip Model for Studying Combinational Vitamin Therapy

Uric acid metabolism promotes apoptosis against Bombyx mori nucleopolyhedrovirus in silkworm, Bombyx mori

Fuyuan Huoxue Decoction Promotes Skin Flap Survival Via the P38MAPK/IKK/NF-κB Pathway in Rats

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